The present invention generally relates to a system and method for determining the extent of spatial organization of atrial activity of the heart. In accordance with additional aspects, the present invention may be utilized to advantage in establishing atrial antiarrhythmic regimens including both appropriate drug screening and selection and chronic electrical cardioverison strategies.
Atrial fibrillation is a common clinical problem, affecting more than one million people in the United States alone, including up to ten percent of those persons over the age of seventy-five. It is the leading cause of cardiogenic embolism and, in the setting of hypertension and/or organic heart disease, is associated with a four to six percent yearly incidents of stroke.
Based upon insights of human studies and animal models, atrial fibrillation is believed to result from rapid and spatially disorganized electrical activity of the atria, with multiple activation wavelets sweeping across the surface of the atria, resulting in an ever-changing pattern of electrical excitation. The absence of coordinated atrial activation and regular, coordinated mechanical contraction, is responsible for the clinical manifestations of atrial fibrillation including loss of hemodynamic efficiency, propensity for thromboembolism, and a rapid, irregular pulse rate.
The preferred clinical end-point for treatment of patients with atrial fibrillation is the restoration and maintenance of normal sinus rhythm with its associated physiologic control of heart rate, preservation of AV synchrony, and reduction of stroke risk. However, this strategy is often frustrated by the inability to prospectively and objectively identify effective antiarrhythmic regimens to prevent recurrences. Additionally, in recent years, the use of antiarrhythmic drugs for atrial fibrillation has been further complicated and attenuated by concerns of potentially life-threatening proarrhythmia associated with empiric drug therapy.
Theoretical consideration, together with results from animal models of atrial fibrillation have suggested that the susceptibility of the atrial electrophysiologic substrate to atrial fibrillation may lend itself to objective, quantitative description. In particular, it has been shown in the dog model that atrial tissue wavelength, .lambda., (equal to the product of conduction velocity and tissue refractory) plays a critical role in establishing the susceptibility of the atria to atrial fibrillation, with short .lambda. predisposing the atrial fibrillation and long .lambda. making atrial fibrillation nonsustainable.
While measurement of .lambda. and drug-induced alterations in .lambda. may provide an objective strategy for the initial selection of antiarrhythmic agents and subsequent measurement of drug effectiveness, its application in the clinical setting is unfortunately impractical. Its practicality is limited due to the inherent technical difficulties associated with the simultaneous measurement of refractoriness and conduction velocity in the intact human heart.
The present invention provides an objective measurement of the spatial organization of atrial fibrillation to provide an objective assessment of the electrophysiologic substrate and its susceptibility to arrhythmia. This is based upon the proposition that the extent of spatial organization of activation during atrial fibrillation is critically dependent upon the atrial tissue wavelength, .lambda.. In accordance with the present invention, the measurement of the spatial organization of atrial fibrillation may be conveniently performed within the clinical setting thus making the procedure advantageous for the provision of an objective strategy for the initial selection of anti-arrhythmia agents and subsequent measurement of drug action in vivo. In addition, the determination of the spatial organization of atrial activity, in accordance the present invention, may further be used to advantage in deriving strategies for the electrical cardioversion of atrial arrhythmias with an implantable atrial defibrillator.